Summary of work: Genomic instability arises from several sources and it is thought to be one of the underlying causes of aging and several age-associated diseases such as cancer. These sources include problems with DNA repair, transcription and replication. We are interested in genomic instability at the population level and how the processes involved in preventing genomic instability may change with aging. This study utilizes sample from subjects enrolled in the Baltimore Longitudinal Study on Aging. Here we measure a number of polymorphisms in DNA repair genes to determine if there are significant changes in the prevalence of each polymorphism with aging or with age-associated diseases. In particular, we have focused on polymorphisms in the gene for the human premature aging disorder, Werner syndrome. Our results so far refute a previous study that showed that patients with a specific Werner mutation have a higher incidence of myocardial infarction. We are currently examining the prevalence in the general population of three other polymorphisms in the Werner gene and other DNA repair genes to ascertain whether they relate to specific clinical conditions. Moreover, we are initiating a follow up study to investigate whether changes in markers of genomic instability associate with age and clinical conditions in cells from the BLSA participants.